Baseline multimodal imaging to predict longitudinal clinical decline in atypical Alzheimer's disease.

There are recognized neuroimaging regions of interest in typical Alzheimer's disease which have been used to track disease progression and aid prognostication. However, there is a need for validated baseline imaging markers to predict clinical decline in atypical Alzheimer's Disease. We aimed to address this need by producing models from baseline imaging features using penalized regression and evaluating their predictive performance on various clinical measures. Baseline multimodal imaging data, in combination with clinical testing data at two time points from 46 atypical Alzheimer's Disease patients with a diagnosis of logopenic progressive aphasia (N = 24) or posterior cortical atrophy (N = 22), were used to generate our models. An additional 15 patients (logopenic progressive aphasia = 7, posterior cortical atrophy = 8), whose data were not used in our original analysis, were used to test our models. Patients underwent MRI, FDG-PET and Tau-PET imaging and a full neurologic battery at two time points. The Schaefer functional atlas was used to extract network-based and regional gray matter volume or PET SUVR values from baseline imaging. Penalized regression (Elastic Net) was used to create models to predict scores on testing at Time 2 while controlling for baseline performance, education, age, and sex. In addition, we created models using clinical or Meta Region of Interested (ROI) data to serve as comparisons. We found the degree of baseline involvement on neuroimaging was predictive of future performance on cognitive testing while controlling for the above measures on all three imaging modalities. In many cases, model predictability improved with the addition of network-based neuroimaging data to clinical data. We also found our network-based models performed superiorly to the comparison models comprised of only clinical or a Meta ROI score. Creating predictive models from imaging studies at a baseline time point that are agnostic to clinical diagnosis as we have described could prove invaluable in both the clinical and research setting, particularly in the development and implementation of future disease modifying therapies.

Association of outer retinal and choroidal alterations with neuroimaging and clinical features in posterior cortical atrophy.

BACKGROUND: Posterior cortical atrophy (PCA) is a rare condition characterized by early-onset and progressive visual impairment. Individuals with PCA have relatively early-onset and progressive dementia, posing certain needs for early detection. Hence, this study aimed to investigate the association of alterations in outer retinal and choroidal structure and microvasculature with PCA neuroimaging and clinical features and the possible effects of apolipoprotein E(APOE) ε4 allele on outer retinal and choroidal alterations in participants with PCA, to detect potential ocular biomarkers for PCA screening. METHODS: This cross-sectional study included PCA and age- and sex-matched healthy control participants from June 2022 to December 2023. All participants with PCA completed a comprehensive neurological evaluation. All participants were recorded baseline information and underwent an ophthalmic evaluation. Quantitative analyses were performed using swept-source optical coherence tomography (SS-OCT) and angiography (SS-OCTA). Adaptive optics scanning laser ophthalmoscopy (AO-SLO) was performed in some patients. In participants with PCA, the influence of APOE ε4 on outer retinal and choroidal alterations and the correlation of outer retinal and choroidal alterations with PCA neuroimaging and clinical features in participants with PCA were investigated. RESULTS: A total of 28 participants (53 eyes) with PCA and 56 healthy control participants (112 eyes) were included in the current study. Compared with healthy control participants, participants with PCA had significantly reduced outer retinal thickness (ORT) (p < 0.001), choriocapillaris vessel density (VD) (p = 0.007), choroidal vascular index (CVI) (p = 0.005) and choroidal vascular volume (CVV) (p = 0.003). In participants with PCA, APOE ε4 carriers showed thinner ORT (p = 0.009), and increased choriocapillaris VD (p = 0.004) and CVI (p = 0.004). The PCA neuroimaging features were positively associated with the ORT, CVI and CVV. Furthermore, differential correlations were observed of PCA clinical features with the CRT, CVV and CVI. CONCLUSIONS: Our findings highlighted the association of outer retinal and choroidal alterations with PCA neuroimaging and clinical features in participants with PCA. Noninvasive SS-OCT and SS-OCTA can provide potential biomarkers for the diagnosis and management of PCA, improving awareness of PCA syndrome among ophthalmologists, neurologists, and primary care providers.

[A case of left posterior cortical atrophy presenting with kana-predominant reading impairment].

The patient was an 85-year-old man with a one-year history of difficulty reading kana. Neuropsychological evaluation revealed kana (phonogram)-selective reading impairment and kanji (ideogram)-dominant writing impairment. MRI revealed significant cerebral atrophy in the left occipital cortex, leading to the clinical diagnosis of posterior cortical atrophy (PCA). Cerebrospinal fluid amyloid ß1-42 levels were reduced, and amyloid PET showed accumulation in the posterior cingulate cortex, precuneus, and frontal lobe. In contrast, tau PET showed no accumulation in the atrophied brain areas. Episodes of REM sleep behavior disorder and decreased uptake on meta-iodobenzylguanidine (MIBG) myocardial scintigraphy suggested the involvement of Lewy body pathology. PCA with distinct laterality has been rarely reported, and |this is the first case to present Kana-selective reading impairment and Kanji-dominant writing impairment with neurodegenerative background.

Exploring experiential differences in everyday activities - A focused ethnographic study in the homes of people living with memory-led Alzheimer's disease and posterior cortical atrophy.

BACKGROUND: Supporting ageing in place, quality of life and activity engagement are public health priorities for people living with dementia, but little is known about the needs and experiences of community-dwelling people with rarer forms of dementia with lesser known symptoms. Posterior cortical atrophy (PCA) is a rare form of dementia usually caused by Alzheimer's disease but which is characterised by diminished visual processing (rather than a dominant memory problem), which poses challenges for maintaining independence and accessing appropriate support. METHODS: This study used a comparative qualitative design and focussed ethnographic methods to explore experiential differences in activity engagement for 10 people with the most common, memory-led presentation of Alzheimer's disease and 10 people with posterior cortical atrophy within their everyday home environments. RESULTS: While the data collection revealed much rich variation in individual and contextual factors, some tentative high-level differences in the experiences of everyday activities could be drawn out, seemingly attributable to the different diagnoses' differing dominant symptoms. These included people with posterior cortical atrophy being less likely to use environmental cues to initiate activities, and more likely to withhold from asking for support because of preserved insight into the impact of this on carers. This lack of initiation of activities could be misinterpreted as apathy. People with posterior cortical atrophy also were discouraged from engaging in activities by disorientation within the home, and difficulties localising, identifying and manipulating objects. People with the more common, memory-led presentation of Alzheimer's disease exhibited more memory-based difficulties with engaging with activities such as forgetting planned activities, where to locate the items required for an activity and the steps involved. Despite these distinct symptom-led challenges, all participants and their family members demonstrated resourcefulness and resilience in making creative adaptations to support continued engagement in everyday activities, supporting the widely reported management strategies of people with dementia of the Alzheimer's type more generally. CONCLUSIONS: These findings offer helpful insights into some the differing impacts dementia related visual and memory impairments can have on everyday activity engagement, which will be helpful for others navigating these challenges and the health and social care practitioners working with people affected by these conditions. The findings also highlight the vast individual variation in the multitude of individual and contextual factors involved in everyday activity engagement, and suggest important areas for future work utilising methods which are similarly high in ecological validity and accessibility as the home-based focussed ethnographic methods utilised here.

Rehabilitation Services for Young-Onset Dementia: Examples from High- and Low-Middle-Income Countries.

The WHO Dementia Global Action Plan states that rehabilitation services for dementia are required to promote health, reduce disability, and maintain quality of life for those living with dementia. Current services, however, are scarce, particularly for people with young-onset dementia (YOD). This article, written by an international group of multidisciplinary dementia specialists, offers a three-part overview to promote the development of rehabilitation services for YOD. Firstly, we provide a synthesis of knowledge on current evidence-based rehabilitative therapies for early-onset Alzheimer's disease (EOAD), behavioural variant frontotemporal dementia (bvFTD), primary progressive aphasia (PPA), and posterior cortical atrophy (PCA). Secondly, we discuss the characteristics of rehabilitation services for YOD, providing examples across three continents for how these services can be embedded in existing settings and the different roles of the rehabilitation multidisciplinary team. Lastly, we conclude by highlighting the potential of telehealth in making rehabilitation services more accessible for people with YOD. Overall, with this paper, we aim to encourage clinical leads to begin introducing at least some rehabilitation into their services, leveraging existing resources and finding support in the collective expertise of the broader multidisciplinary dementia professional community.

The Graded Incomplete Letters Test (GILT): a rapid test to detect cortical visual loss, with UK Biobank implementation.

Impairments of object recognition are core features of neurodegenerative syndromes, in particular posterior cortical atrophy (PCA; the 'visual-variant Alzheimer's disease'). These impairments arise from damage to higher-level cortical visual regions and are often missed or misattributed to common ophthalmological conditions. Consequently, diagnosis can be delayed for years with considerable implications for patients. We report a new test for the rapid measurement of cortical visual loss - the Graded Incomplete Letters Test (GILT). The GILT is an optimised psychophysical variation of a test used to diagnose cortical visual impairment, which measures thresholds for recognising letters under levels of increasing visual degradation (decreasing "completeness") in a similar fashion to ophthalmic tests. The GILT was administered to UK Biobank participants (total n=2,359) and participants with neurodegenerative conditions characterised by initial cortical visual (PCA, n=18) or memory loss (typical Alzheimer's disease, n=9). UK Biobank participants, including both typical adults and those with ophthalmological conditions, were able to recognise letters under low levels of completeness. In contrast, participants with PCA consistently made errors with only modest decreases in completeness. GILT sensitivity to PCA was 83.3% for participants reaching the 80% accuracy cut-off, increasing to 88.9% using alternative cut-offs (60% or 100% accuracy). Specificity values were consistently over 94% when compared to UK Biobank participants without or with documented visual conditions, regardless of accuracy cut-off. These first-release UK Biobank and clinical verification data suggest the GILT has utility in both rapidly detecting visual perceptual losses following posterior cortical damage and differentiating perceptual losses from common eye-related conditions.

Case report: pre-symptomatic clinical and metabolic profile in posterior cortical atrophy and dementia with Lewy bodies.

A research participant was monitored over nearly two decades at Mayo Clinic, undergoing annual neurologic assessments, neuropsychological tests, and multimodal imaging. Initially, he was cognitively normal but developed symptoms consistent with Posterior Cortical Atrophy (PCA) during the study. Early tests indicated mild, yet normal-range declines in language and visuospatial skills. FDG-PET scans revealed increased metabolism in posterior brain regions long before symptoms appeared. Advanced analysis using a novel in-house machine-learning tool predicted concurrent Alzheimer's disease and dementia with Lewy bodies. Autopsy confirmed a mixed neurodegenerative condition with significant Alzheimer's pathology and dense neocortical Lewy bodies. This case underscores the value of longitudinal imaging in predicting complex neurodegenerative diseases, offering vital insights into the early neurocognitive changes associated with PCA and dementia with Lewy bodies.

Age-specific prevalence of the different clinical presentations of AD and FTD in young-onset dementia.

BACKGROUND: Studies have shown that the prevalence of all-variants Alzheimer's disease (AD) and frontotemporal dementia (FTD) both increase with age, even before the age of 65. However, it is not known whether their different clinical presentations all increase in prevalence with age in the same way. METHODS: We studied the prevalence of the different clinical presentations of young-onset AD and FTD by 5-year age groups in a population-based study identifying all dementia patients with a diagnosis of AD and FTD and symptoms onset before age 65 in the Modena province, Italy. By using regression models of cumulative occurrences, we also estimated age-specific prevalence and compared the growth curves of the clinical presentations. RESULTS: The prevalence of all-variants AD increased with age, from 18/1,000,000 in the 40-44 age group to 1411/1,000,000 in the 60-64 age group. The prevalence of all-variants FTD also increased with age, from 18/1,000,000 to 866/1,000,000. An estimation of age-specific prevalence functions of each clinical presentation showed that atypical non-amnestic AD and aphasic FTD grew the most in early ages, followed by the behavioural variant of FTD (bvFTD). Then, around the age of 60, amnestic AD took over and its age-specific prevalence continued to increase disproportionally compared to all the other clinical variants of AD and FTD, which, instead, started to decrease in prevalence. CONCLUSIONS: Amnestic AD is the clinical presentation that increases the most with advancing age, followed by bvFTD, suggesting that there is a differential vulnerability to the effect of ageing within the same neurodegenerative disease.

Peer Support for Caregivers of People Living with Posterior Cortical Atrophy in Melbourne, Australia: A Feasibility Study.

Posterior Cortical Atrophy (PCA) is a rare form of young-onset dementia that causes early visuospatial and visuoperceptual deficits. The symptom profile of Posterior Cortical Atrophy leads to very specific care needs for those affected, who often rely on informal caregivers (including friends and family). Rare dementia support groups can be useful for both patients and their caregivers to assist with knowledge sharing, psychoeducation, and the provision of psychosocial support. Despite this, few such support groups exist. The purpose of this study was to examine a PCA support group for caregivers of individuals living with PCA. We held a structured psychoeducation support group comprised of four sessions with the aim being to provide education, strategies for the management of the disease, and peer support. Caregivers' mental health and quality of life were assessed. The results of our study showed that support group participation was a positive experience and assisted with increasing the knowledge of caregivers and fostering social connections. We suggest that peer support groups may be beneficial for both people living with PCA and their caregivers. We recommend that future quantitative and qualitative research is conducted to further assess health-promotion benefits to people living with PCA and their caregivers, and to assess their development and implementation in different contexts.

Greater white matter degeneration and lower structural connectivity in non-amnestic vs. amnestic Alzheimer's disease.

Introduction: Multimodal evidence indicates Alzheimer's disease (AD) is characterized by early white matter (WM) changes that precede overt cognitive impairment. WM changes have overwhelmingly been investigated in typical, amnestic mild cognitive impairment and AD; fewer studies have addressed WM change in atypical, non-amnestic syndromes. We hypothesized each non-amnestic AD syndrome would exhibit WM differences from amnestic and other non-amnestic syndromes. Materials and methods: Participants included 45 cognitively normal (CN) individuals; 41 amnestic AD patients; and 67 patients with non-amnestic AD syndromes including logopenic-variant primary progressive aphasia (lvPPA, n = 32), posterior cortical atrophy (PCA, n = 17), behavioral variant AD (bvAD, n = 10), and corticobasal syndrome (CBS, n = 8). All had T1-weighted MRI and 30-direction diffusion-weighted imaging (DWI). We performed whole-brain deterministic tractography between 148 cortical and subcortical regions; connection strength was quantified by tractwise mean generalized fractional anisotropy. Regression models assessed effects of group and phenotype as well as associations with grey matter volume. Topological analyses assessed differences in persistent homology (numbers of graph components and cycles). Additionally, we tested associations of topological metrics with global cognition, disease duration, and DWI microstructural metrics. Results: Both amnestic and non-amnestic patients exhibited lower WM connection strength than CN participants in corpus callosum, cingulum, and inferior and superior longitudinal fasciculi. Overall, non-amnestic patients had more WM disease than amnestic patients. LvPPA patients had left-lateralized WM degeneration; PCA patients had reductions in connections to bilateral posterior parietal, occipital, and temporal areas. Topological analysis showed the non-amnestic but not the amnestic group had more connected components than controls, indicating persistently lower connectivity. Longer disease duration and cognitive impairment were associated with more connected components and fewer cycles in individuals' brain graphs. Discussion: We have previously reported syndromic differences in GM degeneration and tau accumulation between AD syndromes; here we find corresponding differences in WM tracts connecting syndrome-specific epicenters. Determining the reasons for selective WM degeneration in non-amnestic AD is a research priority that will require integration of knowledge from neuroimaging, biomarker, autopsy, and functional genetic studies. Furthermore, longitudinal studies to determine the chronology of WM vs. GM degeneration will be key to assessing evidence for WM-mediated tau spread.

Secondary language impairment in posterior cortical atrophy: insights from sentence repetition.

Introduction: Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterized by progressive impairment in visuospatial and perceptual function linked to atrophy of the occipito-parietal cortex. Besides the salient visual impairment, several studies have documented subtle changes in language may also be present. Sentence repetition is a highly constrained linguistic task involving multiple linguistic and cognitive processes and have been shown to be impaired in other AD spectrum disorders, with little consensus on its relevance in PCA. This aim of this study was to further delineate the linguistic and cognitive features of impaired language in PCA using a sentence repetition task. Method: Seven PCA patients and 16 healthy controls verbally repeated 16 sentences from the Boston Diagnostic Aphasia Examination. Responses were transcribed orthographically and coded for accuracy (percentage accuracy; percentage Correct Information Units; Levenshtein Distance) and for temporal characteristics (preparation duration (ms); utterance duration (ms); silent pause duration (ms); speech duration (ms); dysfluency duration (ms)). The potential modulating effects of attentional control and working memory capacity were explored. Results: PCA patients showed lower overall accuracy with retained semantic content of the sentences, and lower phonological accuracy. Temporal measures revealed longer preparation and utterance duration for PCA patients compared to controls, alongside longer speech duration but comparable dysfluency duration. PCA patients also showed comparable silent pause duration to controls. Attentional control, measured using the Hayling sentence completion task, predicted accuracy of sentence repetition. Discussion: The findings suggest that sentence repetition is impaired in PCA and is characterized by phonological, response planning and execution difficulties, underpinned in part by attentional control mechanisms. The emerging profile of language impairment in PCA suggests vulnerability of similar cognitive systems to other Alzheimer's syndromes, with subtle differences in clinical presentation.

Potential ocular indicators to distinguish posterior cortical atrophy and typical Alzheimer's disease: a cross-section study using optical coherence tomography angiography.

BACKGROUND: Posterior cortical atrophy (PCA) is a form of dementia that frequently displays significant visual dysfunction and relatively preserved cognitive and executive functions, thus hindering early diagnosis and treatment. This study aimed to investigate possible fundus markers in PCA patients and compare them with those of typical Alzheimer's disease (AD) patients to seek potential diagnostic patterns. METHODS: Age-matched PCA and AD patients and healthy controls (HC) completed optometry, intraocular pressure measurement, neuropsychologic assessments, optical coherence tomography (OCT), and optical coherence tomography angiography (OCTA) examination in one visit. Overall, six outcomes of thicknesses of various retinal layers and seven outcomes of the retinal microvascular network were calculated. After adjusting for age, sex, and years of education, the OCT and OCTA results were analyzed using analysis of covariance and generalized linear models. Correlation analyses were performed using Spearman correlation, and ROC curves were plotted. RESULTS: Twelve PCA patients, nineteen AD patients, and thirty HC, aged 45-80 years were included. Fifty HC, thirty AD, and twenty PCA eyes were available for foveal avascular zone (FAZ) area analysis; forty-nine HC, thirty-four AD, and eighteen PCA eyes were available for OCT and OCTA assessments. PCA patients had thinner retinal nerve fiber layer and ganglion cell layer + inner plexiform layer than HC in the 0-3 mm circle and 1-3 mm ring. Few structural differences were observed between the AD group and the other two groups. The flow area of the superficial capillary plexus and the intermediate capillary plexus was smaller in the PCA group than in the HC group in the 0-1 mm circle, 0-3 mm circle. MMSE performed better than any combination of optical parameters in identifying AD and PCA from HC (AUC = 1), while the combination of MoCA, retinal thickness and vascular density of ICP in the 1-3 mm ring, with flow area of ICP in the 0-1 mm circle showed the strongest ability to distinguish PCA from AD (AUC = 0.944). CONCLUSIONS: PCA patients exhibited similar impairment patterns to AD patients in the fundus structure and microvascular network. OCTA may aid in the non-invasive detection of AD and PCA, but still remains to be substantiated.

Atypical Alzheimer's disease: new insights into an overlapping spectrum between the language and visual variants.

Overlap between language and visual variants of atypical Alzheimer's disease (AD) has been reported. However, the extent, frequency of overlap, and its neuroanatomical underpinnings remain unclear. Eighty-two biomarker-confirmed AD patients who presented with either predominant language (n = 34) or visuospatial/perceptual (n = 48) deficits underwent detailed clinical examinations, MRI, and [18F]flortaucipir-PET. Subgroups were defined based on language/visual testing and patterns of volume loss and tau uptake were assessed. 28% of the language group had visual dysfunction (marked in 8%), and 47% of the visual group had language impairment (marked in 26%). Progressive involvement of the parieto-occipital and frontal lobes was noted with greater visual impairment in the language group, and greater left parieto-temporal and frontal involvement with worsening language impairment in the visual group. Only 25% of our cohort showed a pure language or visual presentation, highlighting the high frequency of syndromic overlap in atypical AD and the diagnostic challenge of categorical phenotyping.

Altered structural and functional connectivity in Posterior Cortical Atrophy and Dementia with Lewy bodies.

Posterior cortical atrophy (PCA) and dementia with Lewy bodies (DLB) show distinct atrophy and overlapping hypometabolism profiles, but it is unknown how disruptions in structural and functional connectivity compare between these disorders and whether breakdowns in connectivity relate to either atrophy or hypometabolism. Thirty amyloid-positive PCA patients, 24 amyloid-negative DLB patients and 30 amyloid-negative cognitively unimpaired (CU) healthy individuals were recruited at Mayo Clinic, Rochester, MN, and underwent a 3T head MRI, including structural MRI, resting state functional MRI (rsfMRI) and diffusion tensor imaging (DTI) sequences, as well as [18F] fluorodeoxyglucose (FDG) PET. We assessed functional connectivity within and between 12 brain networks using rsfMRI and the CONN functional connectivity toolbox and calculated regional DTI metrics using the Johns Hopkins atlas. Multivariate linear-regression models corrected for multiple comparisons and adjusted for age and sex compared DTI metrics and within-network and between-network functional connectivity across groups. Regional gray-matter volumes and FDG-PET standard uptake value ratios (SUVRs) were calculated and analyzed at the voxel-level using SPM12. We used univariate linear-regression models to investigate the relationship between connectivity measures, gray-matter volume, and FDG-PET SUVR. On DTI, PCA showed degeneration in occipito-parietal white matter, posterior thalamic radiations, splenium of the corpus collosum and sagittal stratum compared to DLB and CU, with greater degeneration in the temporal white matter and the fornix compared to CU. We observed no white-matter degeneration in DLB compared to CU. On rsfMRI, reduced within-network connectivity was present in dorsal and ventral default mode networks (DMN) and the dorsal-attention network in PCA compared to DLB and CU, with reduced within-network connectivity in the visual and sensorimotor networks compared to CU. DLB showed reduced connectivity in the cerebellar network compared to CU. Between-network analysis showed increased connectivity in both cerebellar-to-sensorimotor and cerebellar-to-dorsal attention network connectivity in PCA and DLB. PCA showed reduced anterior DMN-to-cerebellar and dorsal attention-to-sensorimotor connectivity, while DLB showed reduced posterior DMN-to-sensorimotor connectivity compared to CU. PCA showed reduced dorsal DMN-to-visual connectivity compared to DLB. The multimodal analysis revealed weak associations between functional connectivity and volume in PCA, and between functional connectivity and metabolism in DLB. These findings suggest that PCA and DLB have unique connectivity alterations, with PCA showing more widespread disruptions in both structural and functional connectivity; yet some overlap was observed with both disorders showing increased connectivity from the cerebellum.

Atypical clinical variants of Alzheimer's disease: are they really atypical?

Alzheimer's disease (AD) is a neuropathological disorder defined by the deposition of the proteins, tau and ß-amyloid. Alzheimer's disease is commonly thought of as a disease of the elderly that is associated with episodic memory loss. However, the very first patient described with AD was in her 50's with impairments in multiple cognitive domains. It is now clear that AD can present with multiple different non-amnestic clinical variants which have been labeled as atypical variants of AD. Instead of these variants of AD being considered "atypical," I propose that they provide an excellent disease model of AD and reflect the true clinical heterogeneity of AD. The atypical variants of AD usually have a relatively young age at onset, and they show striking cortical tau deposition on molecular PET imaging which relates strongly with patterns of neurodegeneration and clinical outcomes. In contrast, elderly patients with AD show less tau deposition on PET, and neuroimaging and clinical outcomes are confounded by other age-related pathologies, including TDP-43 and vascular pathology. There is also considerable clinical and anatomical heterogeneity across atypical and young-onset amnestic variants of AD which reflects the fact that AD is a disease that causes impairments in multiple cognitive domains. Future studies should focus on careful characterization of cognitive impairment in AD and consider the full clinical spectrum of AD, including atypical AD, in the design of research studies investigating disease mechanisms in AD and clinical treatment trials, particularly with therapeutics targeting tau.

Visual Agnosia Mimicking Memory Impairment: A Case Report of Posterior Cortical Atrophy.

Vision specialists will benefit from increased awareness of posterior cortical atrophy (PCA) syndrome. Failure to adequately identify the chief complaint as a visual symptom may lead to incorrect diagnosis or diagnostic delay. A previously healthy, 59-year-old woman presented with a 5-year history of 'losing her stuff'. Upon psychiatric and neuro-ophthalmological evaluation, this symptom was better recognised as a feature of visual agnosia and simultanagnosia. She also presented with multiple previously unrecognised symptoms indicative of higher visual processing dysfunction, such as alexia without agraphia, ocular motor apraxia, optic ataxia, prosopagnosia, akinetopsia and topographagnosia, so further assessment to investigate for PCA was carried out. After a work-up including cognitive assessment, brain structural/functional imaging, and laboratory tests she was diagnosed with visual-variant Alzheimer's disease. Patients with PCA merit a detailed review of their symptoms, as well as the use of office tests such as cognitive evaluation tools, different types of perimetry, colour vision tests, and non-delayed psychiatric consultation for correct management and assessment. This report will emphasise five key aspects to be considered when evaluating patients with PCA.

Ventral Variant Posterior Cortical Atrophy with Occipito-temporal Accumulation of Tau Proteins/Astrocyte Gliosis.

A 73-year-old woman with posterior cortical atrophy (PCA) presented with progressive apperceptive visual agnosia, alexia, agraphia, ventral simultanagnosia, prosopagnosia, and allocentric (stimulus-centered) left-sided hemispatial neglect. All of these symptoms were attributed to damage to the bilateral occipito-temporal cortices, consistent with ventral variant PCA. While the Pittsburgh compound B uptake was extensively distributed throughout the occipito-parietal (dorsal) and occipito-temporal (ventral) areas, the THK5351 (ligand binding to tau aggregates/astrocyte gliosis) accumulation was limited to the ventral area. These findings suggest that local accumulation of tau proteins and/or astrocyte gliosis over the occipito-temporal cortices can result in ventral variant PCA.

Neurophysiological Alterations of the Visual Pathway in Posterior Cortical Atrophy: Systematic Review and a Case Series.

Background: The clinical features of posterior cortical atrophy (PCA), a rare condition often caused by Alzheimer's disease, have been recently defined, while little is known about its neurophysiological correlates. Objective: To describe neurophysiological alterations of the visual pathway as assessed using visual field test (VF), visual evoked potentials (VEP), and electroretinogram (ERG) in PCA patients. Methods: Studies reporting VF, VEPs, and ERG in PCA patients were selected according PRISMA method. Of the 323 articles that emerged from the literature, 17 included the outcomes of interest. To these data, we added those derived from a patient cohort enrolled at our clinic. Results: The literature review included 140 patients, half of them (50%) presented with homonymous hemianopia or quadrantanopia. VEPs were available in 4 patients (2 normal findings, 1 decreased amplitude, and 1 increased latency) and ERG in 3 patients (substantially normal findings). Our case series included 6 patients, presenting with homonymous lateral hemianopia in 50% and contralateral cortical atrophy. VEPs showed normal amplitude in 66-83% according to the stimulation check, and increased latency in 67% in absence of myelin damage on MRI. Latency was increased in both eyes in 50% and only on one side in the other 50%. Such alterations were observed in patients with more severe and symmetric atrophy. ERG showed normal findings. Conclusions: Neurophysiological investigations of the visual pathway in PCA are almost absent in literature. Alterations involve both amplitude and latency and can be also monocular. A multiple-point involvement of the optical pathway can be hypothesized.